Often, the first step in microbial (e.g., bacterial and bacterial spore, fungal and viral) infection (e.g., of animals) is attachment or colonization of skin or mucus membranes, followed by subsequent invasion and dissemination of the infectious microbe.
B. anthracis, a gram-positive, non-motile, spore-forming bacterium, is the etiological agent of anthrax. Spores from B. anthracis are extremely resistant to a wide range of adverse environmental conditions, such as heat, ultraviolet and ionizing radiation, and chemical agents (See, e.g., Mock and Fouet. Annu. Rev. Microbiol 2001; 55:647-671). B. anthracis Ames strain is very lethal, 100 spores is equal to one LD50 (50% lethal dose). With the emergence of B. anthracis spores as a weapon of terror (See, e.g., Jernigan et al. Emer. Inf. Dis. 2001; 7:933-933), it is important to develop new vaccines to prevent and new therapies to control B. anthracis infections. The anthrax vaccine currently licensed for human use in the United States is composed of a sterile culture supernatant of an attenuated pXO1+, pXO2 B. anthracis strain. This undefined nature of the components and the requirement for six immunizations over 18 months followed by annual boosters also suggests a need for improved, alternative vaccines or treatments.
While an anthrax vaccine is available (See e.g., Ivins et al., Vaccine 13:1779 (1995)) and can be used for the prevention of classic anthrax, genetic mixing of different strains of the organism can render the vaccine ineffective (See e.g., Mobley, Military Med. 160:547 (1995)). The potential consequences of the use of Anthrax spores as a biological weapon was demonstrated by the accidental release of B. anthracis from a military microbiology laboratory in the former Soviet Union. Seventy-seven cases of human anthrax, including 66 deaths, were attributed to the accident. Some anthrax infections occurred as far as 4 kilometers from the laboratory (See e.g., Meselson et al., Science 266:1202 (1994)). Genetic analysis of infected victims revealed the presence of either multiple strains or a genetically altered B. anthracis (See e.g., Jackson et al., Proc. Nat. Acad. of Sci. U.S.A. 95:1224 (1998)).
Additionally, other members of the genus Bacillus are also reported to be etiological agents for many human diseases. Bacillus cereus is a common pathogen. It is involved in food borne diseases due to the ability of the spores to survive cooking procedures. It is also associated with local sepsis and wound and systemic infection (See e.g., Drobniewski, Clin. Micro. Rev. 6:324 (1993)). Many bacteria readily develop resistance to antibiotics. An subject infected with an antibiotic-resistant strain of bacteria faces serious and potentially life-threatening consequences.